There is great interest in changes in the properties of the cell membrane as a primary event in neoplastic transformation. Changes in the activity of adenylate cyclase are often encountered in transformed or neoplastic cells and a number of other membrane properties appear to derive from the changes in cyclic nucleotide metabolism. eg. agglutinability by lectins, rate of cell division, motility and adhesiveness. Other properties (eg. contact inhibition and the appearance of new antigens) do not appear to be derivitive to changes in cyclic nucleotide metabolism. Thus a change in adenylate cyclase activity though clearly important is probably not the sole causative event in neoplastic transformation. Information about the regulation of cyclic nucleotide metabolism is of real value in the study of cancer cell biology and also the cyclic nucleotide related enzymes are excellent loci for studying the determinants of plasma membrane protein composition and the interaction between intrinsic and extrinsic proteins of the plasma membrane. The activity of the light regulated cyclic GMP phosphodiesterase of the photoreceptor disc membrane is intimately coupled to the physical state of rhodopsin and thus provides unique opportunities to study interaction of proteins of known function within or on a well characterized membrane. In addition to studying the details of the regulation of a principal determinant of cyclic nucleotide metabolism (phosphodiesterase), we plan to study other related intrinsic (eq. guanylate cyclase) and extrinsic membrane proteins (eg. cyclic GMP binding protein and protein kinase) of the disc membrane. We plan to structurally characterize these proteins and also study the nature of their interactions in or on the membrane. The disc phosphodiesterase (Mw approximately 180,000 daltons) is an extrinsic protein which, although clearly coupled to rhodopsin (whose state of illumination regulates phosphodiesterase activity), can nevertheless be eluted from and restored to the disc membrane with full recovery of enzyme activity.